Fruit and lung cancer.
Total fruit and lung cancer risk.
About the male analysis: In 2003 a pooled analysis of 8 prospective studies was published (Smith-Warner SA [24]). The analysis included data from a total of
1,808 men of which 298 were from The ATBC Study. In 2002 another publication about The ATBC Study included data from 1,644 men (Holick CN [18]), which is nearly as
much as the total amount of cases from the pooled analysis. A similar finding was done with The Netherlands Cohort Study. For this systematic review it was chosen not
to include data about men from the pooled analysis as a whole, but from the individual cohorts, because this allowed for a much larger amount of cases in the analysis.
As a consequence of this decision, data about men from The New York State Cohort (including 392 male cases) can not be included in these specific parts of the review,
since no article is published about this specific cohort.
Results:
- Men & women combined: 34 articles, providing information about 20 different cohorts were found, including 14,323 cases. Significant protective effects
were found in 6 cohorts (Knekt P [8], Balder HF [11], Holick CN [18], Linseisen J [19], Neuhouser ML [22], George SM [29]), 2 of which were of very large size (19, 29).
These 6 cohorts included 8.752 cases (61% of all cases). In addition, nonsignificant protective effects were found in a pooled analysis of 6 cohorts
(Smith-Warner SA [24]), an in one additional cohort (Alavanja MC [27]), including another 1,445 cases (10% of all cases). No other (non)significant associations were
found.
The average RR = 0.85 (excluding incomplete data from Shekelle RB [1], Ratnasinghe D [15]). - Men: Data was provided about 11 cohorts including a total of 8,116 cases. A significant protective association was found in 4 cohorts
(Knekt P [8], Balder HF [11], Holick CN [18], George SM [29]) including 7,300 cases (90% of all cases), and a nonsignificant protective effect was found in one other
study (Shekelle RB [1]). No associations were found in the remaining 6 cohorts).
The average RR = 0.87 (excluding incomplete data from Shekelle RB [1], Ratnasinghe D [15]). - Women: Data was provided about 9 cohorts including a total of 3,862 cases. A nonsignificant protective effect was found in a pooled analysis of 6 cohorts
(Smith-Warner SA [24]), and a nonsignificant protective effect was found in one other cohort (Alavanja MC [27]) including 1,445 cases. No other associations were found,
but all RRs were < 1.
The average RR = 0.86 - In 4 cohorts including a total of 2,345 cases, risk was not stratified by sex. Significant protective effects were found in 1 cohort (Linseisen J [19]), and in the placebo arm of another cohort (Neuhouser ML [22]), including 1,452 cases. No other associations were found. The average RR = 0.80
Inclusion of intermediate levels of consumption:
Though a fair amount of (non) significant associations were found, sometimes the trend, but not the effect (RR) was (non)significantly differend from 1.00.
(Non)significant effects at any level of consumption among men were as follows:
- Knekt P (8) Significant at the highest tertile of consumption. This was defined as 106 g/day, but it is not clear if this was the median intake or the lower boundary from the range.
- Balder HF (11) Significant at ≥ 88 g/day.
- Holick CN (18) Significant at 127-188 g/day.
(Non)significant effects at any level of consumption among men were as follows:
- Smith-Warner SA Significant at the 2nd-3rd quintile of consumption, and nonsignificant at the 5th quintile of consumption. No levels of consumption could be defined, because the pooled analysis included study-specific quintiles of consumption from the 6 cohorts.
A clear level of consumption for a protective effect is hard to define, because few RR's differed significantly from 1. But a protective effect may allready be
found from consumption of ≥ 127 g/day.
The figure below includes effects from male and/or female cohorts with at least 500 lung cancer cases.
Results from cohorts with ≥ 500 cases:
Effect modification by variables other than sex and smoking status:
No evidence of effect modification was found by age of diagnosis, or by the number of fruit and vegetable questions included on a study's FFQ
(Smith-Warner SA [24]). And no evidence of effect modification was found by alcohol intake or multivitamin use (Feskanich D [14]).
But in one cohort, the protective effect of fruit was restricted to non-users of beta carotene/vitamin A supplements (Neuhouser ML [22]).
Conclusion: For men & women combined, significant protective effects were found in 6 cohorts, 2 of which were of very large size. These cohorts included
a majority of the total amount of cases (61%), and no (non)significantly increased risks were found. The effect was of moderate size (- 15%). Total fruits consumption
probably protects against lung cancer risk. Stratified by sex, total fruits consumption probably protects against lung cancer risk among men, while the evidence was
only suggestive for a protective effect among women. But since the effect sizes were similar for men and women (- 13, and - 14%, respectively), no heterogeneity
in effects seems to exist. The level of consumption for a protective effect is hard to define, but may allready be found at moderate consumption (≥ 127 g/day).
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 29) George SM (2008) | The NIH-AARP Diet and Health Study | 4,092 | RR = 0.91 (0.81-1.01; P = 0.05) |
| 27) Alavanja MC (2004) | The Agricultural Health Study | 213 | OR = 0.9 (0.5-1.4; P = 0.64) |
| 18) Holick CN (2002) | The ATBC Study | 1,644 | RR = 0.87 (0.74-1.02; P = 0.01) |
| 15) Ratnasinghe D (2000) | No cohort name | 106 | No association (P = 0.49) |
| 14) Feskanich D (2000) | The Health Professionals' Follow-up Study | 258 | RR = 1.22 (0.87-1.87) |
| 11) Balder HF (2005) | The Netherlands Cohort Study | 1,426 | RR = 0.69 (0.53-0.91; P = 0.001) |
| 8) Knekt P (1999) | The Finnish Mobile Clinic Health Cohort | 138 | RR = 0.58 (0.37-0.93; P = 0.013) |
| 5) Jansen MC (2004) | The Zutphen Elderly Study | 42 | RR = 0.58 (0.26-1.29; P = 0.17) |
| 4) Shibata A (1992) | The Leisure World Study | 94 | RR = 0.99 (0.59-1.66) |
| 2) Kvale G (1983) | No cohort name | 70 | RO = 1.10 (P = 0.90) |
| 1) Shekelle RB (1981) | The Western Electric Study | 33 | An inverse association (P = 0.073) |
| Total number of cases: 8,116 | Average RR = 0.87 |
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 29) George SM (2008) | The NIH-AARP Diet and Health Study | 2,347 | RR = 0.89 (0.77-1.02; P = 0.163) |
| 27) Alavanja MC (2004) | The Agricultural Health Study | 47 | OR = 0.6 (0.2-1.6; P = 0.09) |
| 24) Smith-Warner SA (2003) | Pooled analysis of 6 studies | 1,398 | RR = 0.83 (0.70-1.00; P = 0.07) |
| 4) Shibata A (1992) | The Leisure World Study | 70 | RR = 0.68 (0.37-1.24) |
| Total number of cases: 3,862 | Average RR = 0.86 |
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 25) Liu Y (2004) | The JPHC Study | 428 | RR = 1.16 (0.84-1.58) |
| 23) Takezaki T (2003) | No cohort name defined | 51 | RR = 0.61 (0.29-1.30; P = 0.227) |
| 22) Neuhouser ML (2003) | The CARET Study | 326 (placebo), and 414 (intervention) | Placebo arm: RR = 0.56 (0.39-0.81; P = 0.003). Intervention arm: RR = 0.79 (0.57-1.11; P = 0.13) |
| 19) Linheisen J (2007) | The EPIC Study | 1,126 | HR = 0.75 (0.59-0.96) |
| Total number of cases: 2,345 | Average RR = 0.80 |
Total fruit and lung cancer risk. Stratified by smoking status.
Background:
About the analysis: For this systematic review, data is stratified by smoking status into current smokers, former smokers, and never smokers.
The JPHC Study (Liu Y [25]) and CARET Study (Neuhouser M [22]) provided data about "ever smokers" without stratifying into former vs current smokers. Likewise,
The Finnish Mobile clinic Health Cohort (Knekt P [8]) provided data about "current nonsmokers" without stratifying into nonsmokers vs former smokers. It was chosen not
to include this data in the following tables.
About the analysis of current smokers: In 2003 a pooled analysis of 8 prospective studies was published (Smith-Warner SA [24]). The analysis included data from a
total of 1,915 smoking cases of which 298 were from The ATBC Study. In 2002 another publication about The ATBC Study included data from 1,644 smoking cases (Holick CN [18]),
which is nearly as much as the total amount of cases from the pooled analysis. For the systematic review it was chosen not to include data about current smokers from
the pooled analysis as a whole, but from the individual cohorts, because this allowed for a much larger amount of cases in the analysis.
Results:
- Current smokers: Data about current smokers was provided by 8 cohorts, including 6,251 cases. Significant protective effects were found in 3 cohorts of moderate-very large size, including 2,943 cases (47% of all cases). No other (non)significant associations were found. The average RR = 0.86
- Former smokers: Data about former smokers was provided by a pooled analysis of 7 cohorts, and 2 additional cohorts. No (non)significant associations were found, but all RR's were < 1. The average RR = 0.90
- Never smokers: Data about never smokers was provided by a pooled analysis of 7 cohorts, and 3 additional cohorts. No (non)significant associations were found. The average RR = 0.94
Conclusion: Among current smokers, significant protective effects were found in 3 cohorts, including 47% of all cases. Suggestive evidence was found for a protective effect of total fruits against lung cancer risk among current smokers (- 14%). No evidence was found for an association among former or never smokers.
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 29) Wright ME (2008) | The NIH-AARP Diet and Health Study | 1,583 men, and 1,196 women | Men: RR = 0.84 (0.69-1.04; P = 0.12). Women: RR = 0.95 (0.78-1.17; P = 0.58). |
| 19) Linseisen J (2007) | The EPIC Study | 731 | HR = 0.72 (0.52-0.99) |
| 18) Holick CN (2002) | The ATBC Study | 1,644 | RR = 0.87 (0.74-1.02; P = 0.01). |
| 14) Feskanich D (2000) | The Health Profesional's Follow-up Study & The Nurses' Health Study | 86 men, and 269 women | Men: 1.54 (0.76-3.13). Women: RR = 0.89 (0.59-1.35). |
| 11) Voorrips LE (2000) | The Netherlands Cohort Study | 568 | RR = 0.7 (0.4-1.0; P = < 0.0001). |
| 10) Steinmetz KA (1993) | The Iowa Women's Health Study | 81 | OR = 0.95 (0.46-1.96; P = 0.7). |
| 8) Knekt P (1991) | The Finnish Mobile Clinic Health Cohort | 93 | RR = 0.98 (P = 0.89) for low vs high consumption. |
| Total number of cases: 6,251 | Average RR = 0.86 |
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 29) Wright ME (2008) | The NIH-AARP Diet and Health Study | 2,110 men, and 835 women | Men: RR = 0.91 (0.79-1.05; P = 0.36). Women: RR = 0.94 (0.75-1.17; P = 0.85). |
| 24) Smith-Warner SA (2003) | Pooled analysis of 7 studies | 981 | RR = 0.85 (0.69-1.05; P = 0.43) |
| 19) Linseisen J (2007) | The EPIC Study | 291 | HR = 0.93 (0.59-1.48) |
| Total number of cases: 4,217 | Average RR = 0.90 |
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 29) Wright ME (2008) | The NIH-AARP Diet and Health Study | 141 men, and 170 women | Men: RR = 0.81 (0.46-1.41; P = 0.35). Women: RR = 1.08 (0.64-1.84; P = 0.99). |
| 25) Liu Y (2004) | The JPHC Study | 106 | RR = 2.09 (0.56-7.83; P = 0.22) |
| 24) Smith-Warner SA (2003) | Pooled analysis of 7 studies | 259 | RR = 0.59 (0.34-1.04; P = 0.16) |
| 19) Linseisen J (2007) | The EPIC Study | 98 | HR = 0.59 (0.25-1.38) |
| Total number of cases: 774 | Average RR = 0.94 |
Total fruit and lung cancer mortality.
11 articles, providing information about 9 different cohorts were found. The dietary assessement was conducted following cancer diagnosis, in one cohort only
(Skuladottir H [19]).
Results:
- Men: Data was provided about 7 cohorts including 4,057 cases. Significant protective effects were found in 5 cohorts
(Wang LD [3], Jansen MC [5], Ozasa K [17], Appleby PN [20], Sauvaget C [21]) including 3,797 cases (94% of all cases). RRs were well below 1 in both remaining cohorts.
Risk was often presented in frequency of consumption (times or days/week: 3, 9, 17, 20, 21). And significant protective effects were found at (almost) daily consumption in 4 of these cohorts (3, 17, 20, 21). The average RR = 0.60 - Women: Data was provided about 3 cohorts. No (non)significant effects were found, but RRs were < 1.
- Two other cohorts did not stratify risk by sex. No significant effects were found, but RRs were < 1.
Conclusion: Significant protective effects were found in 5 cohorts - one of which of very large size. These 5 cohorts included a total of
84% of all cases. In addition, all RRs were below 1.
Total fruit probably protects against lung cancer mortality. Stratified by sex, (almost) daily consumption of total fruits probably protects against lung cancer
mortality among men (- 40%), while no associations were found among women.
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 26) Khan MM (2004) | No cohort name | 41 | RR = 0.8 (0.3-2.2) |
| 21) Sauvaget C (2003) | The Hiroshima/Nagasaki Life Span Study | 345 | A significant protective effect (RR = 0.68) |
| 20) Appleby PN (2002) | The Health Food Shoppers Study | 51 | RR = 0.47 (0.27-0.84; P = < 0.05) |
| 17) Ozasa K (2001) | The JACC Study | 300 | HR = 0.73 (0.55-0.97; P = 0.049) |
| 9) Chow WH (1992) | The Lutheran Brotherhood Study | 219 | RR = 0.7 (0.4-1.3) |
| 5) Jansen MC (2001) | The Seven Countries Study | 149 | RR = 0.69 (0.46-1.02; P = 0.05) |
| 3) Wang LD (1985) | No cohort name | 2,952 | MR = 1.75 for low vs high consumption. |
| Total number of cases: 4,057 | Average RR = 0.60 |
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 21) Sauvaget C (2003) | The Hiroshima/Nagasaki Life Span Study | 175 | No association |
| 20) Appleby PN (2002) | The Health Food Shoppers Study | 30 | RR = 0.65 (0.31-1.35) |
| 17) Ozasa K (2001) | The JACC Study | 84 | HR = 0.80 (0.42-1.50; P = 0.66) |
| Total number of cases: 289 |
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 19) Skuladottir H (2006) | The Danish Diet, Cancer and Health Study | Not defined | A nonsignificant protective effect: HR = 0.81 (0.58-1.15) |
| 16) Breslow RA (2000) | The NHIS | 154 | RR = 0.9 (0.5-1.6; P = 0.489) |
| Total number of cases: 154 + X |
| Author | Cohort name | Subjects | Years of follow-up | Cases | End point | Consumption of | Relative Risk (RR) | Adjustments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 29) George SM (2008) | The National Institutes of Health-AARP Diet and Health Study. | 195,229 women and 288,109 men aged 50-71. (USA) | 1995-2003 | 2,347 women, and 4,092 men | Lung cancer incidence | Fruit |
1 cup = 237 mL. One cup is 1 cup of raw/cooked fruit, 1 cup of 100% juice, or 0.5 cup of dried fruit. Age, smoking (smoking status, time since quitting, and smoking dose), energy intake, BMI, alcohol, physical activity, education , race, marital status, family history, menopausal hormone therapy (women), and vegetable intake. |
29) Wright ME (2008) | The NIH-AARP Diet and Health Study | 472,081 subjects (281,288 men and 190,793 women) aged 50-71. | (USA) 8 | (1995-2003) See variables | Lung cancer risk | Total fruits (apples, apple sauce, pears, bananas, dried fruit excluding apricots, peaches, nectarines, plums, cantaloupe, other melons, strawberries, oranges, tangerines, tangelos, grapefruit, grapes, orange and grapefruit juice, and other fruit juices and drinks) |
All men (3,834 cases): | RR = 0.91 (0.82-1.02; P = 0.10) for the highest vs lowest quintile of consumption. Amount specific data (servings per 1000 kcal per day): < 0.65: RR = 1. 0.65-1.08: RR = 0.98 (0.89-1.07). 1.09-1.56: RR = 0.91 (0.83-1.01). 1.57-2.27: RR = 0.95 (0.86-1.06). > 2.27: RR = 0.91 (0.82-1.02).
All women (2,201 cases): RR = 0.97 (0.84-1.11; P = 0.70) for the highest vs lowest quintile of consumption. Amount specific data (servings per 1000 kcal per day): < 0.89: RR = 1. 0.89-1.41: RR = 0.96 (0.85-1.09). 1.42-1.97: RR = 0.97 (0.86-1.11). 1.98-2.76: RR = 0.98 (0.86-1.12). > 2.76: RR = 0.97 (0.84-1.11).
One serving of fruits = 1 medium sized fresh fruit, 1/2 cup of chopped fruit, or 6 ounces of fruit juice. Adjustment for vegetables did not alter the associations. There were no differences when fruit intake was examined with respect to the different histological types of lung cancer in either sex. Age, energy intake, race, education, BMI, smoking status, time since quitting, past smoking dose (former smokers only), current smoking dose (current smokers only), alcohol intake, physical activity, and family history of any cancer. |
27) Alavanja MC (2004) | The Agricultural Health Study Cohort. | 57,284 pesticide applicators and 32,333 spouses of farmer applicators from Iowa and North Carolina. | 6.2 | (1993-97 to 2001) See variables | Lung cancer incidence | Fruits (not defined) |
|
Age, smoking status, sex, race, state of residence, education, pneumonia, other chronic lung disease (bronchitis and emphysema), asthma, family history of lung cancer, vegetables, alcohol intake. |
25) Liu Y (2004) | The JPHC Study | 2 cohorts with 42,224 (aged 40-59) and 51,114 (aged 40-69) subjects. | (Japan) Cohort I: 10 (1990-1999). | Cohort II: 7 (1993-1999) 428 | (329 men, 99 women) (198 adenocarcinomas, 176 non-adenocarcinomas) (106 never smokers, 317 ever smokers) lung cancer risk | Fruit (Cohort I: one item (not defined). | Cohort II: apples; citrus)
RR = 1.16 (0.84-1.58; No P-value) for the highest vs lowest tertile of consumption. | Amount specific data (pooled tertiles not defined): T1: RR = 1. T2: RR = 1.08 (0.64-1.81). T3: RR = 1.16 (0.84-1.58). Very high vs very low consumption: No association was found when fruits were categorized into six groups of consumption (no data shown).
Findings did not differ when analysis were limited to men (data not shown) Age, gender, area, sports, frequency of alcohol intake, BMI, vitamin supplement use, salted fish and meat, pickled vegetables, smoking duration, and number of cigarettes per day among ever smokers. |
24) Smith-Warner SA (2003) | Pooled analysis of 8 prospective studies. | 430,281 (280.419 women and 149.862 men) | 6-16 | 3,206? | (1,398 women and 1,808 men) (259 never smokers, 981 past smokers, 1,915 current smokers) (956 adenocarcinomas [581 women, 375 men], 538 small cell carcinomas [256 women, 282 men], 901 squamous cell carcinomas [242 women, 659 men]) Lung cancer risk | Total fruits (Fruits and fruit juice. The number of items varied from 6 to 26 across studies.) |
INCLUSION CRITERIA: |
INCLUDED STUDIES (Follow-up years/No. of lung cancer cases):
RELATIVE RISK:
RR categorized into deciles: 0.68 (0.56-0.83; No P-value). RR using identical absolute cutpoints across studies: 0.82 (0.68-0.98; No P-value) for intakes of ≥ 400 vs < 100 g/day.
The test for heterogeneity among studies was not significant for total fruits, total vegetables or total fruits and vegetables, indicating that the differences in relative risks across the studies were compatible with random variation. There was no evidence of effect modification by the number of fruit and vegetable questions included on a study's food frequency questionnaire. Adjusted for education, BMI, alcohol intake, calories, smoking status, smoking duration for past/current smokers, amount smoked for current smokers. Results were similar after further adjustment for multivitamin use. Simultaneous adjustment for total fruit and total vegetable intakes did not materially alter the results observed when each group was analyzed separately. |
23) Takezaki T (2003) | No cohort name defined. | 5,885 residents (2,798 males and 3,087 females) aged 40-79 from Aichi Prefecture. | (Japan) 1985-1999 | 51 | Lung cancer incidence | Fruit (not defined) |
RR = 0.61 (0.29-1.30; P = 0.227) for the highest vs lowest tertile of consumption. | Amount specific data (times/wk): < 3: RR = 1. 3-4: RR = 0.97 (0.52-1.79). ≥ 5: RR = 0.61 (0.29-1.30). Age, sex, smoking, and occupation. |
22) Neuhouser ML (2003) | The Beta-carotene And Retinol Efficacy Trial (CARET) (2003) | 14,120 current or former heavy smokers (male/female) and asbestos-exposted workers (male) aged 50-69. | 12 | (1989-2001) 742? | (326 in placebo arm, and 414 in intervention arm) Primary lung cancer risk | Total fruits (apples, applesauce, pears, peaches, apricots, nectarines, strawberries, oranges, grapefruit, banana, berries, papaya, mango, orange juice, grapefruit juice and other juices) |
|
Non-small cell lung cancers: A significant 40% reduced risk was found in the placebo group (214 cases), but not in the intervention arm (281 cases). Sex, age, smoking status, total pack-years of smoking, asbestos exposure, race-ethnicity, and enrollment center. |
19) Raaschou-Nielsen O (2008) | The Danish Diet, Cancer and Health Study (DCH) | 56,488 individuals aged 50-64. | 1994-97 to 2003 | 430 | Lung cancer risk | Fruit (not defined) | The median dietary intake of fruit was lower among cases (123 g/day) than among sub-cohort members (175 g/day). | Unadjusted. |
19) Linseisen J (2007) | The EPIC Study | 478,590 individuals, mostly aged 25-70 from 10 European countries. | 6.4 | (1992-2000) 1,126 (608 men, 518 women), of which 731 current smokers, 291 former smokers, and 98 never smokers) | lung cancer risk | Fruit (all fresh and dried fruits, excluding nuts and seeds and olives) |
HR = 0.75 (0.59-0.96) for the highest vs lowest quintile of consumption. | Amount specific data (g/day): 0-89.7: HR = 1. 89.7-154.7: HR = 0.98 (0.83-1.16). 154.7-238.3: HR = 0.84 (0.70-1.02). 238.3-356.8: HR = 0.94 (0.77-1.15). 356.8-4645.6: HR = 0.75 (0.59-0.96).
Since results were not significantly different between men and women, no sex-stratified results are presented. adjusted for tobacco smoking (status and duration), education (5 categories), physical activity at work (5 categories), intake of red meat, intake of processed meat, height, weight, nonfat energy intake, energy intake from fat, ethanol intake at baseline |
19) Sorensen M (2007) | The Danish Diet, Cancer and Health Study (DCH). | 56,488 subjects aged 50-64. | 1994-97 to 2003 | 430 | Lung cancer incidence | Fruit (e.g. apples, oranges, bananas, pears and peaches) | Cases consumed less fruit (122 g/day) than sub-cohort members (175 g/day; P = < 0.001). | Unadjusted. |
19) Sorensen M (2006) | The Danish Diet, Cancer and Health Study. | 56,488 individuals aged 50-64. | 1994-97 to 2003 | 431 | Lung cancer incidence | Fruit (e.g. apples, oranges, bananas, pears and peaches) | The median dietary intake of fruit was lower among cases (122 g/day) than among sub-cohort members (175 g/day). | Age. |
19) Skuladottir H (2004) | The Danish Diet, Cancer and Health Study. | 54,158 (aged 50-64) | 1993-2001 | 247 | (142 men and 105 women) (43 small cell carcinoma, 79 adenocarcinoma, 49 squamous cell carcinoma) lung cancer risk | Fruit (16 varieties of fruit [Not defined]. The most frequently consumed fruits were apples, pears and oranges. Excluding fruit juices) |
RR = 0.86 (0.59-1.26; No P-value) for the higest vs lowest quartile of consumption. | Amount specific data (g): 5-40: RR = 1. 41-88: RR = 1.21 (0.86-1.76). 89-164: RR = 1.00 (0.69-1.44). 165-643: RR = 0.86 (0.59-1.26).
Age, smoking status, duration of smoking, number of cigarettes/day and occupation. |
19) Miller AB (2004) | The EPIC Study. | 335,376 individuals, mostly aged 25-70 from 7 European countries (excluding Germany, France and Greece) | 1992-98 to 1998-2002 | 860 (532 smokers, 236 ex-smokers, and 88 never smokers) | lung cancer risk | Total fruits (defined as: all fresh and dried fruit items, including citrus fruits; all nuts and seeds, nut spread; mixed nuts and raisins, fruit cocktail, fruit salad; olives. Not fruit juices), and | Fruits (defined as: all fresh and dried fruit items, including citrus fruits. Not fruit juices)
|
Smoking, height and stratified by sex and centre. |
19) Miller AB (2002) | The EPIC Study | 127,892 men and 289,946 women. | 4 | 247? men and 245? women | Lung cancer incidence | All fruits (not defined) |
HR = 0.78 (0.58-1.04) for the highest vs lowest quartile of consumption. | Amount specific data (Quartiles not defined): Q1: HR = 1. Q2: HR = 0.81 (0.63-1.04). Q3: HR = 0.80 (0.62-1.04). Q4: HR = 0.78 (0.58-1.04). Stratified by centre and gender and adjusted for time of follow-up and smoking. |
18) Holick CN (2002) | The Alpha-tocopherol, Beta-carotene Cancer Prevention Study (ATBC). | 27,084 white male smokers (≥ 5 cigarettes/day) aged 50-69. | (Finland) 14 | (1985-1998) 1,644 | Lung cancer incidence | Fruit (not defined) |
RR = 0.87 (0.74-1.02; P = 0.01) for the highest vs lowest quintile of consumption. | Amount specific data (g per day): < 45: RR = 1. 45-84: RR = 1.00 (0.86-1.16). 85-126: RR = 1.00 (0.87-1.16). 127-188: RR = 0.82 (0.70-0.96). > 188: RR = 0.87 (0.74-1.02). Age, years smoked, cigarettes per day, intervention (alpha-tocopherol, and beta-carotene supplements), supplement use (beta-carotene and vitamin A), energy intake, cholesterol and fat. |
18) Hirvonen T. (2001) | The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. | 27,110 male smokers aged 50-69. | (Finland) mean 6.1 | (1985-1993) 791 | Lung cancer risk | Fruits (not defined) |
RR = 0.73 (0.60-0.90; P = 0.005) for the highest vs lowest quartile of consumption. | Amount specific data (g/day): < 32: RR = 1. 32-70: RR = 0.91 (0.76-1.1). 71-120: RR = 0.91 (0.75-1.1). > 120: RR = 0.73 (0.60-0.90). This association became nonsignificant in a multivariate model including vegetables, berries, tea and wine). Age, supplementation group, years of smoking, and number of cigarettes/day. |
15) Ratnasinghe D (2000) | Cohort name not defined. | 9,142 men aged 41-79 who were miners in the Yunnan Tin Corporation. | (China) 6 | (1992-1997) 108 | (of which 2 women) Lung cancer risk | Total fruit (not defined) | Lung cancer cases did not consume less fruit (83 g/day) than controls (79 g/day; P = 0.49). | Unadjusted. |
14) Feskanich D (2000) | The Nurses' Health Study | & The Health Professionals' Follow-up Study 77,283 US women (38-63 years) and 47,778 men (40-75 years) | Women: 1984-1996. | Men: 1986-1996. 516 women (54 never smokers, 193 past smokers, 269 current smokers/ 179 Kreyberg I, 232 Kreyberg II), and | 258 men (24 never smokers, 148 past smokers, 86 current smokers/ 120 Kreyberg I, 93 Kreyberg II) Total lung cancer risk | Total fruit (defined as: raisins/grapes; prunes; bananas; cantaloupe; watermelon; apples/pears; apple juice; oranges; orange juice; grapefruit; grapefruit juice; other fruit juices; strawberries; blueberries; peaches/apricots/plums) |
MEN: | RR = 1.22 (0.80-1.87) for the highest vs lowest quintile of consumption. Amount specific data (servings/day): < 1.1: RR = 1. 1.1-1.7: RR = 1.18 (0.80-1.73). 1.8-2.3: RR = 1.30 (0.88-1.92). 2.4-3.3: RR = 1.23 (0.82-1.84). > 3.3: RR = 1.22 (0.80-1.87).
WOMEN: A nonsignificantly lower risk: RR = 0.76 (0.56-1.02) for the highest vs lowest quintile of consumption. Amount specific data (servings/day): < 1.1: RR = 1. 1.1-1.7: RR = 1.03 (0.80-1.32). 1.8-2.3: RR = 0.84 (0.64-1.12). 2.4-3.1: RR = 0.98 (0.74-1.29). > 3.1: RR = 0.76 (0.56-1.02). Variety: Risk of lung cancer remained reduced for both variety (≥ 6 vs < 2 fruits. RR = 0.81; 95% CI = 0.55-1.20) and frequency (RR = 0.87; 95% CI = 0.60-1.28), suggesting that both factors contribute to a lower risk of cancer.
MEN & WOMEN: It is possible that earlier diet plays a more critical role in the etiology of lung cancer. To examine this possibility, we used various lag times between the diet measure and follow-up. For both fruits and vegetables, a higher intake was not associated with a lower risk of lung cancer in men and was only weakly associated with a lower risk in women when diet was measured within 4 years of diagnosis. However, when a longer lag time was applied, inverse associations became apparent in both cohorts:
Effect modification: Other analyses stratified by age, alcohol intake, and multivitamin use provided no evidence of a modification of effect. In both cohorts, associations between intake of fruits and vegetables and the risk of lung cancer were similar for participants over 65 years old and those 65 years old or younger, for abstainers and for drinkers of one or more drinks per day, and for current users and nonusers of multivitamins. Risks for never smokers are adjusted for age, follow-up cycle, total energy intake, and availability of diet data after baseline. In addition, risks for past smokers are adjusted for years since quitting, risks for current smokers are adjusted for cigaretts smoked/day, and risks for both past and current smokers are adjusted for age at start of smoking. |
Other covariates (i.e., BMI, physical activity, alcohol consumption, and use of multivitamin supplements) did not remain in the final models because they did not affect the RRs. 11) Hogervorst JG (2009) | The Netherlands Cohort Study on Diet and Cancer | 58,279 men and 62,573 women aged 55-69. | 13,3 | (1986-2000) 2649? | Lung cancer incidence | Fruit (not defined) |
Case subjects, regardless of the type of lung cancer that they had, consumed less fruit than subcohort members. |
Unadjusted. |
11) Balder HF (2005) | The Netherlands Cohort Study | 58,279 men aged 55-69. | 9.3 | (1986-1995) 1,426 | Lung cancer risk | Total fruits (not defined, but including citrus fruit, bananas, apples/pears, and [straw]berries) |
RR = 0.69 (0.53-0.91; P = 0.001) for the highest vs lowest quintile of consumption. | Amount specific data (g/d): 31: RR = 1. 88: RR = 0.77 (0.59-0.99). 135: RR = 0.67 (0.52-0.87). 186: RR = 0.63 (0.48-0.83). 290: RR = 0.69 (0.53-0.91). Adjusted for age at baseline, total energy intake, current cigarette smoker, number of cigarettes smoked per day, years of smoking cigarettes, higher vocational or university education, family history of lung cancer, physical activity, and BMI |
11) Voorrips LE (2000) | The Netherlands Cohort Study | 62,573 women and 58,279 men aged 55-69. | 6.3 | (1986-1992) 963 | (62 never smokers, 331 former smokers, 568 current smokers) (611 male Kreyberg I, 150 male Kreyberg II, 77 female Kreyberg I, and 44 female Kreyberg II) lung cancer risk | Total fruit (defined as: mandarins; oranges and fresh orange juice; grapefruits and fresh grapefruit juice; grapes; bananas; apples, pears; strawberries. Excluding other fruit juices) |
RR = 0.8 (0.6-1.1; P = < 0.0001) for the highest vs lowest quintile of consumption. | Amount specific data (g/day): 46: RR = 1. 109: RR = 0.7 (0.6-1.0). 157: RR = 0.6 (0.5-0.8). 216: RR = 0.6 (0.4-0.8). 325: RR = 0.8 (0.6-1.1). Additional adjustment for total vegetable intake did not change results at all (No data shown).
age, sex, family history of lung cancer, highest educational level, current smoker, years of smoking, number of cigarettes/day. |
10) Hayes JH (2006) | The Iowa Women's Health Study. | 27,162 women ages 61-75. | 1992-2002 | 403? | Lung cancer incidence | Total fruit (not defined) | HR = 0.58 (0.47-0.71; P = < 0.0001) for ≥ 17 servings/week (median). | Unadjusted. |
10) Olson JE (2002) | The Iowa Women's Health Study. | 38,006 women aged 55-69. | 1986-1998 | 553 | Lung cancer incidence | Fruit (not defined) |
RR = 0.80 (0.61-1.06; P = 0.03) for the highest vs lowest quintile of consumption. | Amount specific data (servings/week): ≤ 10: RR = 1. 10.1-14.5: RR = 0.67 (0.51-0.87). 14.6-19.0: RR = 0.88 (0.69-1.12). 19.1-25.5: RR = 0.68 (0.52-0.88). > 25.5: RR = 0.80 (0.61-1.06). Age, smoking status, and pack-years of smoking. |
10) Steinmetz KA (1993) | The Iowa Women's Health Study. | 35,115 women aged 55-69. | 4 | (1986-1989) 138? | Lung cancer incidence | All fruit (Raisins or grapes; prunes; bananas; cantaloupe; watermelon; fresh apples or pears; oranges; grapefruit; strawberries; blueberries; peaches, apricots, or plums; blackberries; cherries; currants; dates; fruit cocktail; guavas; honeydew melon; kiwi fruit; lemons; limes; mangoes; crenshaw melon; nectarines; persimmons; pineapple; plantains; pomegranates; quince; raspberries; tangerines; applesauce; and dried apples. apricots. bananas, currants, figs, nectarines, papaya, peaches, and pineapple) |
OR = 0.75 (0.44-1.23; P = 0.08) for the highest vs lowest quartile of consumption. | Amount specific data (servings/wk): ≤ 7: OR = 1. 8-11: OR = 0.80 (0.50-1.28). 12-17: OR = 0.51 (0.29-0.88). ≥ 18: OR = 0.75 (0.44-1.23).
Age, energy intake, and pack-years of smoking. |
8) Knekt P (1999) | The Finnish Mobile Clinic Health Examination Survey. | 4545 men aged 20-69. | 25 | (1967-72 to 1991) 138? | Lung cancer risk | Fruits (not defined) |
RR = 0.58 (0.37-0.93; P = 0.013) for the highest vs lowest tertile of consumption. | Amount specific data (Tertiles): T1: RR = 1. T2: RR = 0.85 (0.57-1.25). T3: RR = 0.58 (0.37-0.93). Tertiles are defined as "Low" (39 g/day) and "High" (106 g/day). Age and smoking status. |
8) Knekt P (1993) | The Finnish Mobile Clinic Health Cohort | 5,254 men aged ≥ 15. | (2,590 non/ex-smokers & 2,664 smokers. Nested case-control) 19 | (1968-72 to ?) 121? | Lung cancer risk | Fruits and berries (not defined) |
|
Age. |
8) Knekt P (1991) | The Finnish Mobile Clinic Health Cohort | 4,538 men aged 20-69 (2,121 nonsmokers, and 2,417 smokers). | 20 | (1966-72 to 1986) Non/ex-smokers: 24? | Current smokers: 93? Lung cancer risk | Fruits and berries (not defined) |
|
Age. |
Results were not changed after adjustment for social class, geographic area, energy and fat intake, BMI, height, or all other foodstuffs. 7) Fraser GE (1991) | The Adventist Health Study | 34,198 white California seventh-day adventists. | (USA) 6 | (1977-1982) 52 | Lung cancer risk | Fruit (not defined) |
RR = 0.26 (0.10-0.70; P = 0.006) for the highest vs lowest tertile of consumption. | Amount specific data (times): < 3/week: RR = 1. 3-7/week: RR = 0.30 (0.16-0.58). ≥ 2/day: RR = 0.26 (0.10-0.70).
Age, sex, and smoking history |
5) Jansen MC. (2004) | The Zutphen Elderly Study | (Part of The Seven Countries Study). 730 men aged 65-84. | (The Netherlands) 10 | (1985-1995) 42 | Lung cancer risk | Fruit (strawberries, berries, grapes, peaches, cherries, prunes, and apricots) |
|
Age, smoking-status, pack-years of cigarette smoking, total energy intake, physical activity, BMI, alcohol intake, fruit intake, and vegetable intake when variety studied. |
5) Ocké MC (1997) | The Zutphen Study | (the Dutch contribution to The Seven Countries Study) 561 men. | 20 | (1971-1990) 54? | Lung cancer incidence | Fruits (citrus fruits, other fruits, apple compote, and cooking pear) |
|
Age, pack-years of cigarettes, and energy intake. |
4) Shibata A (1992) | The Leisure World Study. | 5,080 elderly men. | (USA) 8 | (1981-1989) 97 | Lung cancer risk | All fruits (defined as: cantaloupe, mangos; watermelon; apricots, nectarines [include apricot nectar]; peaches; papayas; persimmons; sour cherries; prunes, prune juice; apples, applesauce [not apple juice]; bananas; avocados, guacamole; pineapple, pineapple juice; blackberries, blueberries, raspberries, boysenberries, loganberries, sweet cherries; fruit cocktail; oranges, tangerines, mandarin oranges, orange juice; white grapefruit and juice; pink/red grapefruit and juice; honeydew, casaba melons; strawberries; cranberry juice cocktail; plums; rhubarb; grapes, pears, figs, raisins, dates) |
RR = 1.24 (0.73-2.10;No P-value) for the highest vs the lowest tertile of consumption. | Amount specific data (Tertiles not defined): T1: RR = 1. T2: RR = 1.49 (0.91-2.44). T3: RR = 1.24 (0.73-2.10). age, personal, and wife's smoking-adjusted |
4) Shibata A. (1992) | The Leisure World Study. | 11,580 residents of a retirement community. | (USA) 1981-1989 | 164 (94 men, 70 women) | Lung cancer risk | Fruits (Cantaloupe, mangos, watermelon, apricots, nectarines [including apricot nectar], peaches, papayas, persimmons, sour cherries, prunes, prune juice, apples, applesauce [not apple juice], bananas, avocados, guacamole, pineapple, pineapple juice, blackberries, blueberries, raspberries, boysenberries, loganberries, sweet cherries, fruit cocktail, oranges, tangerines, mandarin oranges, orange juice, white grapefruit and juice, pink/red grapefruit and juice, honeydew, casaba melons, strawberries, cranberry juice cocktail, plums, rhubarb, grapes, pears, figs, raisins, dates) |
|
Age and smoking. |
Adjustment for BMI or physical activity did not materially alter the results (data not shown). 2) Kvale G (1983) | No cohort name. | 10,602 men. | (Norway) 11.5 | (1967-1978) All: 70. | Squamous and small cell: 43. Lung cancer risk | Fruits and berries (not defined) |
|
Age, cigarette smoking, region and urban/rural place of residence. |
1) Shekelle RB (1981) | The Western Electric Study. | 1954 men aged 40-55. | 19 | (1957-?) 33? | Lung cancer incidence | Fruit (not defined) | Fruit tended to be inversely related to the risk of lung cancer (P = 0.073). | Unadjusted. |
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